Bianchi et al. in Eur. J. Med. Chem.--Chimica Therapeutica 16(4), 321-326 (1981) discloses benzimidazolino2-on derivatives having anti-ulcer and anti-secretory activity. Clark et al. in J. Med. Chem. 21(9), 965-978 (1978) discloses imidazo[4,5-b]pyridin-2-on derivatives having analgesic activity.
European patent application Publication No 477819 discloses related compounds which are openers of BK channels.
It is generally well known that opening of potassium (K+) channels leads to a hyperpolarization and relaxation of cells. The presently known K+ channel openers (e.g. cromakalim and pinacidil) exert their effect primarily via the K+ channel subtype K.sub.ATP. They have a high affinity for vascular smooth muscle cells and are thus mostly vasodilators. Recent studies indicate, however, that K+ channel openers hyperpolarizing neuronal cells also have anticonvulsive and antiischemic effects in the central nervous system (the CNS) (European Journal of Pharmacology 167, 181-183 (1989), Neuroscience Letters 115, 195-200 (1990), Neuroscience 37(1), 55-60 (1990), The Journal of Pharmacology and Experimental Therapeutics 251 (1), 98-104 (1989)). Furthermore recent studies demonstrate that potassium channel openers acting on airways smooth muscle (tracheal smooth muscle) cells will have anti-asthmatic effects (Williams et al., The Lancet 336, 334-336 (1990).
There exist other K+ channel subtypes than K.sub.ATP, and one such subtype is the BK channel, also called the maxi-K channel or large-conductance, Ca.sup.2+ dependent K+ channel. The BK channel is present in many cells including most central and peripheral nerve cells, striated muscle cells, smooth muscle cells of the airways, the vasculature, the gastrointestinal tract and bladder, in endo- and exocrine glands including pancreatic .beta.-cells and in kidney tubules (R. Latorre et al., Annu. Rev. Physiol. 51, 385 (1989).
A scorpion toxin peptide, charybdotoxin, which blocks the BK channel fairly specifically, has been used to demonstrate that the BK channel plays an important role as a relaxing negative feed-back when the cells in these tissues become highly active or spastic (J. E. Brayden and M. T. Nelson, Science 256, 532 (992; T. R. Jones et al., J. Pharmacol. Exp. Ther. 255, 697 (1990); R. Robiteille and M. P. Charlton, J. Neurosci. 12, 297 (1992); G. Suarez-Kurtz et al., J. Pharmacol. Exp. Ther. 259, (1991)).